Roflumilast increases clara cell secretory protein in cigarette smoke-exposed mice

Xiao Na Ge, Hong Wei Chu, Maisha N. Minor, Stephanie R. Case, David G. Bosch, Richard J. Martin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Decreased Clara cell secretory protein (CCSP) levels have been found in smokers and chronic obstructive pulmonary disease (COPD) patients, which may be related to the development of COPD. A phosphodiesterase-4 (PDE4) inhibitor, roflumilast, appears to have therapeutic value for COPD. However, its effect on CCSP in cigarette smoke (CS)-exposed lungs has not been investigated. AKR/J mice were treated as follows: air control, CS, roflumilast plus CS, and roflumilast. Mice underwent four weeks of air or CS exposure. Roflumilast was administrated at 5mg/kg via gavage once daily for the duration of the study. CCSP levels in bronchoalveolar lavage (BAL) fluid and ERK1/2 activation in lungs were examined. CS exposure tended to decrease CCSP levels in BAL fluid compared to air controls. Treatment with roflumilast significantly reversed CS-induced downward trend of CCSP in BAL fluid. Roflumilast significantly inhibited CS-induced upward trend of ERK1/2 activation in lungs, and the levels of activated ERK1/2 in lungs negatively correlated with CCSP levels of BAL fluid in CS, and CS plus roflumilast groups. Our results demonstrate that one of the therapeutic mechanisms of roflumilast is to reverse CS-induced downward trend in CCSP levels of BAL fluid, which may be mediated by down-regulating ERK1/2 activity.

Original languageEnglish (US)
Pages (from-to)185-191
Number of pages7
JournalCOPD: Journal of Chronic Obstructive Pulmonary Disease
Issue number3
StatePublished - 2009

Bibliographical note

Funding Information:
This study was financially supported by ALTANA Pharma AG (now part of Nycomed Group), Konstanz, Germany. Additionally, R.J. Martin serves on advisory boards for AstraZeneca, Schering, and Teva. Keywords: Cigarette smoke, Clara cell secretory protein, ERK1/2, phosphodiesterase-4 inhibitor, roflumilast Correspondence to: Richard J. Martin National Jewish Medical and Research Center 1400 Jackson Street J206 Denver Colorado, 80206, USA phone: 1 3033981545 fax: 1 3032702139 email:


  • Cigarette smoke
  • Clara cell secretory protein
  • ERK1/2
  • Phosphodiesterase-4 inhibitor
  • Roflumilast

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